Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates lymphangiogenesis and angiogenesis. This system is partially responsible for the restoration of the oxygen supply to tissues when blood circulation is inadequate. VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, in muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. VEGF is a sub-family of growth factors, namely the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both lymphangiogenesis and angiogenesis.
When VEGF is overexpressed, it can contribute to various disease conditions. Solid cancers cannot grow beyond a limited size without an adequate blood supply, and thus cancers that can express VEGF are able to grow and metastasize. Overexpression of VEGF can also cause vascular disease in the retina of the eye and other parts of the body. Drugs such as bevacizumab have been used in an attempt to inhibit VEGF and control or slow those diseases.
Members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (the VEGFRs) on the cell surface, causing them to dimerize and become activated through transphosphorylation, although to different sites, times and extents. The VEGF receptors have an extracellular portion consisting of 7 immunoglobulin-like domains, a single transmembrane spanning region, and an intracellular portion containing a split tyrosine-kinase domain. VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well-defined, although it is thought to modulate VEGFR-signaling.